The ABO(H) blood group antigens appear to become dedifferentiated or are incompletely developed in many cases of cancer, particularly carcinomas characterized by marked anaplasia or by metastatic lesions. We will examine tissues from appropriate tumors and their normal tissue counterparts which will be extracted and assayed on a quantitative basis by means of hemagglutinin inhibition and agglutinin absorption. The results will be compared with studies or smears and histologic sections of tissue using the mixed cell agglutination reaction and peroxidase or ferritin antibody labelling methods. In order to confirm that blood group deficits are in fact losses, and not indicative of a disease-induced masking phenomenon, we will repeat the latter studies using sections of enzyme treated tissue. Biochemical approaches to this problem will be developed in either event. True antigen losses probably reflect alterations in the metabolic pathway of the specific immunodeterminant sugar responsible for the individuals blood group. We therefore plan to test appropriately processed case material for deficient blood group transferase (synthetic) enzymes, for evidence of deficient cell surface acceptors, or for possible excesses of specific catabolic enzymes. Blood specimens will be similarly tested in the event that metabolic alterations, if present, will be reflected generally. In the event that masking proves an explanation for some blood group "losses", we will search for increases in transferase enzymes corresponding to the substances which appear to cause this phenomenon; for example, sialyl transferase in the case of sialic acid. The possible usefulness of some of these tests in cancer prognosis and diagnosis will be determined in serial patient investigations.